Antimicrobial polymeric compositions

ABSTRACT

A compound having the formula: 
     
       
         
         
             
             
         
       
         
         
           
             wherein n, y, R 1  and R 2  are defined herein, and others, methods of making of and using, and compositions made thereby which have an antimicrobial resistance effect are described.

REFERENCE TO EARLIER APPLICATIONS

This application claims priority to U.S. Provisional Application SerialNos. 61552452, filed Oct. 27, 2011, and 61552454, filed Oct 27, 2011.

GOVERNMENT LICENSE RIGHTS

This invention was made with government support under DMR grantsDMR-0207560 DMR-0802452, and DMR-1206259 awarded by the National ScienceFoundation and Office of Naval Research Grant #000140-81-09-2-2 awardedby the Office of Naval Research. The government has certain rights inthe invention. National Science Foundation (DMR-grants DMR-0207560,DMR-0802452, and DMR-1206259), the Office of Naval Research (Grant#000140-81-09-2-2) and the VCU School of Engineering Foundationsupported this research.

FIELD OF THE APPLICATION

The present application relates to polymer compositions which impartmicrobial resistance.

BACKGROUND

Infection acquired from health care environments is one of the leadingmajor medical complications in the present world. Studies have shownthat almost 6% of patients admitted to hospitals acquire infections andthe number of such cases is increasing. According to reports by the USCenter of Disease Control that hospital acquired infections account formore than 2 million cases leading to 99,000 deaths annually.

The most common hospital acquired infections include urinary tractinfections, surgical wound infections and those associated withintravascular cannulas. The mode of transmission of these infections ismostly by physical contact with infected medical devices. Staphylococcusaureus, Pseudomonas aeruginosa, and Escherichia coli are the most commonbacterial isolates that give rise to these infectious diseases. It hasbeen observed that most of the bacterial strains develop resistance toantibiotics over a period of time. In the hospital environment, over 50%of Staphylococcus aureus have developed resistance to methicillin, whichultimately leads to surgical wound infection and catheter relatedsepsis. Some of the emerging antibiotic resistant pathogens includevancomycin resistant enterococci, vancomycin intermediatestaphylococcus, and multiple antibiotic resistant Gram negativeorganisms like acinetobacter, enterobacter and mycobacterium.

Biocidal polymers offer promise in helping curb the spread of infectionsby providing coatings for applications such as biomedical devices ormolded articles. An antimicrobial avoids adhesion and proliferation ofplanktonic microbes on the surface by either repelling or killing themicrobes. While repelling surfaces can be achieved by creatingultrahydrophobic surfaces, the killing of microbes can be achieved byeither biocide release or contact kill. In some instances release andcontact kill are combined. Contact antimicrobial function isaccomplished by covalently bonding the biocide; thereby, promisingdurability. Because contact kill precludes the biocide entering thebacterial metabolic processes, elimination of bacterial resistancebuildup may result. Interest in contact kill has led to a number ofstudies on polymers with covalently bound alkylammonium groups.

Contact kill silicone coatings include a class of biocidal polysiloxaneswith 3-(alkyldimethylammonium)propyl pendant groups. Antimicrobialactivity of PDMS chains terminated with quaternary ammoniumfunctionalities bearing oxyethylene moieties has been studied. In ahumid environment, these oxyethylene chains spread out, exposing theammonium moieties which imparts biocidal property to these compounds.Simultaneously, cationic silicones have also been used as surfacemodifiers, one of them being a reactive silane,(MeO)₃Si(CH₂)₃N⁺Me₂C₁₈H₃₇Cl⁻ (DC 5700). This compound, developed by DowCorning, renders bactericidal properties to surfaces like glass, cotton,polyester fibers.

Quaternary function (sometimes referred to herein as “quat”) has beenintroduced into PDMS coatings using R_(quat)Si(OR)₃ and condensationcure. With trifunctional R_(quat)Si(OR)₃ competition must occur betweenquaternary function in the bulk (crosslinker) and at the surface.Accordingly, 10-15 weight percent R_(quat)Si(OR)₃ was required to obtainmodest antimicrobial activity, which is undesirable due to expense.

Cationic surface active polyurethane surface modifiers as antimicrobialcoatings have been previously studied. Examples include HMDI-BD basedpolyurethanes such as shown in FIG. 1 as the polymer surface modifiercontaining a random P[AB] copolyoxetane soft block, where A is afluorine based oxetane (3FOx) and B contains a quaternary ammonium sidechain(C12) with a twelve membered carbon chain. HMDI is H₁₂MDI,(4,4′-(methylene bis-(p-cyclohexyl isocyanate)) and BD is 1,4-butanediol have been used for hard blocks in studies for antimicrobialcoatings.

A small percentage of this modifier polyurethane was blended with aHMDI-BD-PTMO polyurethane (base polyurethane) which is commonly used invarious industrial applications. It was observed that the resultingP[AB] polyurethane, when blended with an HMDI-BD-PTMO polyurethane,exhibited excellent antimicrobial properties. However, the surfaceactive charge was not stable, and the antimicrobial property decreaseddrastically after two weeks.

Betaines are a specialized family of zwitterion that comprise both acationic moiety and anionic functional groups. Various betaines haveshown good antibacterial activity and a broad scope of inhibition. Inprevious studies, betaines were introduced into to the polymer backbonethrough ether, amide, imide, or other hydrolysable chemical bonds.However, these suffered from leaching from the substrate and decreasingantibacterial activity during use. The antibacterial agentsiloxanesulfopropylbetaine (SSPB) with a reactive alkoxysilane group forthe finishing of cotton textiles has been previously studied.

BRIEF DESCRIPTIONS OF THE FIGURES

FIG. 1 shows one embodiment of a conventional composition,HMDI-BD(30)-P[(3FOx)(C12)-86:13-M_(n)]

FIG. 2 presents biocidal tests described in the examples.

FIG. 3 shows one embodiment of P[AB] copolyoxetane polyurethane PSM;soft block “brush” surface concentration; and base polyurethane.

FIG. 4 shows one embodiment of a conventional composition PSMMDI/BD-P[(3FOx)(MEnOx)-p:(1-p)], 27-42 hard block wt %, and baseMDI/BD(36)-PTMO(2200).

FIG. 5 presents biocidal test results.

FIG. 6 presents one embodiment of an exemplary composition and resultsobserved therefor.

FIG. 7 presents zeta potential results described in the examples.

FIG. 8 presents zeta potential results described in the examples.

FIG. 9 presents antimicrobial results for an exemplary composition.

FIG. 10 presents antimicrobial results for an exemplary composition.

FIG. 11 presents one embodiment of end capping a diol.

FIG. 12 presents zeta potential results described in the examples.

FIG. 13 presents one embodiment for preparation of the quaternaryammonium modifier and a representative modified PDMS coating.

FIG. 14 presents embodiments of condensation reactions.

FIG. 15 presents test results described in the examples.

FIG. 16 presents biocidal test results described in the examples.

FIG. 17 presents test results described in the examples.

FIG. 18 presents test results described in the examples.

FIG. 19 presents biocidal test results described in the examples.

FIG. 20 presents mechanical test results described in the examples.

FIG. 21 presents one embodiment of a synthetic route of DAPMDS-PDMS.

FIG. 22 presents one embodiment of a synthetic route of DAPMDS-PDMS-PS.

FIG. 23 presents biocidal test results described in the examples.

BRIEF SUMMARY OF THE SEVERAL EMBODIMENTS

One embodiment provides a polyoxetane diol having the formula:

-   -   wherein n is 0 to 1;    -   wherein y is an integer of 1-1000; and    -   wherein R₁ and R₂ are not identical and are each independently        —OCH₂CF₂H, —OCH₂CF₂CF₂H, —OCH₂CF₂CF₂CF₂H, —Br,        —(OC₂H₄)_(x)—O—CH₃, wherein x is 0-11, alkoxy, fluoroalkoxy,        alkoxycycloalkyl, or a group having one of the following        formulas:

wherein a is 5-15;

wherein b is 0-5

wherein X is Cl, Br, I, OH, or NO₃; and

wherein A is —CO₂ or —SO₃.

In one embodiment, the polyoxetane diol may have one of the followingformulas:

One embodiment provides a polymer, comprising a polymerization productof:

-   -   (A) the polyoxetane diol;    -   (B) one or more of an isocyanate, diisocyanate, or combination        thereof;    -   (C) optionally, a diol or diamine chain extender; and    -   (D) optionally, a soft block diol selected from the group        polydimethylsiloxane diol, polytetramethylene oxide diol,        polypropylene oxide diol, polyethylene oxide diol, polybutadiene        diol, polyisobutylene diol, perfluorinated diol, or a        combination of two or more thereof.

In one embodiment, the isocyanate may have the formula:

so that a compound having the following formula is produced:

-   -   wherein n is 0 to 1;    -   wherein y is an integer of 1-1000; and    -   wherein R₁ and R₂ are not identical and are each independently        —OCH₂CF₂H, —OCH₂CF₂CF₂H, —OCH₂CF₂CF₂CF₂H, —Br,        —(OC₂H₄)_(x)—O—CH₃, wherein x is 0-11, alkoxy, fluoroalkoxy,        alkoxycycloalkyl, or a group having one of the following        formulas:

wherein a is 5-15;

wherein b is 0-5

wherein X is Cl, Br, I, OH, or NO₃; and

wherein A is —CO₂ or —SO₃.

One embodiment provides an end-capped compound having the formula:

-   -   wherein n is 0 to 1;    -   wherein y is an integer of 1-1000; and    -   wherein R₁ and R₂ are not identical and are each independently        —OCH₂CF₂H, —OCH₂CF₂CF₂H, —OCH₂CF₂CF₂CF₂H, —Br,        —(OC₂H₄)_(x)—O—CH₃, wherein x is 0-11, alkoxy, fluoroalkoxy,        alkoxycycloalkyl, or a group having one of the following        formulas:

wherein a is 5-15;

wherein b is 0-5

wherein X is Cl, Br, I, OH, or NO₃; and

wherein A is —CO₂ or —SO₃.

In one embodiment, the end-capped compound may have one of the followingformulas:

One embodiment provides a composition, comprising a polymerizationproduct of:

-   -   (A) the end-capped compound;    -   (B) one or more bis(trialkoxysilyl)alkanes having the formula:

-   -   wherein R_(D) is —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, or —CH₂CH₂CH₂CH₃;        and wherein r is an integer of 1-10;

or one or more polydialkoxysiloxanes having the formula:

-   -   where R is —CH₃ or —C₂H₅;    -   (C) one or more of an isocyanate, diisocyanate, or combination        thereof;    -   (D) optionally, a diol or diamine chain extender; and    -   (E) optionally, a soft block diol selected from the group        consisting of polydimethylsiloxane diol, polytetramethylene        oxide diol, polypropylene oxide diol, polyethylene oxide diol,        or a combination of two or more thereof.

In one embodiment, (B) may have the formula:

One embodiment provides a composition, comprising:

-   -   (a) a reaction product of:        -   (A) the end-capped compound; and        -   (B) one or more bis(trialkoxysilyl)alkanes having the            formula:

-   -   wherein R_(D) is —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, or —CH₂CH₂CH₂CH₃;        and wherein r is an integer of 1-10;

or one or more polydialkoxysiloxanes having the formula:

-   -   where R is —CH₃ or —C₂H₅;    -   and    -   (b) a polymerization product of:        -   (C) one or more of an isocyanate, diisocyanate, or            combination thereof;        -   (D) optionally, a diol or diamine chain extender; and        -   (E) optionally, a soft block diol selected from the group            consisting of polydimethylsiloxane diol, polytetramethlene            oxide diol, polypropylene oxide diol, polyethylene oxide            diol, polydimethylsiloxane dipropylamine, or a combination            of two or more thereof.

The composition may be either a blend, copolymer, or crosslinkedcopolymer matrix. In one embodiment, the composition is a blend of (a)and (b).

One embodiment provides a difunctional surface modifying agent, havingthe formula:

-   -   wherein R¹, R², R³, R⁶, R⁷, R⁸ are each independently hydrogen,        alkyl, alkenyl, cycloalkyl, or aryl;    -   wherein each R⁴ is independently a —CR⁹R¹⁰— group wherein R⁹ and        R¹⁰ are each independently hydrogen or alkyl;    -   wherein each R⁵ is independently a —CR⁹R¹⁰— group wherein R⁹ and        R¹⁰ are each independently hydrogen or alkyl;    -   wherein X is anion, Cl, Br, I, OH, or NO₃;    -   wherein n is 1-20; and    -   wherein m is 1-20.

In one embodiment, the difunctional surface modifying agent has theformula:

One embodiment provides a method of making the difunctional surfacemodifying agent, comprising reacting a compound having the formula:

with a compound having the formula:

to produce the surface modifying agent.

In one embodiment, the reactants for the surface modifying agent havethe respective following formulas:

One embodiment provides a polymer, comprising a polymerization productof:

-   -   (A) the difunctional surface modifying agent;    -   (B) a soft block diol selected from the group        polydimethylsiloxane diol, polytetramethylene oxide diol,        polypropylene oxide diol, polyethylene oxide diol, polybutadiene        diol, polyisobutylene diol, perfluorinated diol, or a        combination of two or more thereof; and    -   (C) optionally, one or more bis(trialkoxysilyl)alkanes having        the formula:

-   -   wherein R_(D) is —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, or —CH₂CH₂CH₂CH₃;        and

wherein r is an integer of 1-10;

or one or more polydialkoxysiloxanes having the formula:

-   -   where R is —CH₃ or —C₂H₅;

In one embodiment, (A) is a compound having the formula:

-   -   (B) is a polydimethylsiloxane diol; and    -   (C) is a compound having the formula:

One embodiment provides a polymer, comprising a polymerization productof:

-   -   (A) a compound having one of the following formulas:

-   -   wherein k is 1-4;    -   and wherein A is —CO₂ or —SO₃;    -   (B) a soft block diol selected from the group        polydimethylsiloxane diol, polytetramethylene oxide diol,        polypropylene oxide diol, polyethylene oxide diol, polybutadiene        diol, polyisobutylene diol, perfluorinated diol, or a        combination of two or more thereof; and    -   (C) optionally, one or more bis(trialkoxysilyl)alkanes having        the formula:

-   -   wherein R_(D) is —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, or —CH₂CH₂CH₂CH₃;        and

wherein r is an integer of 1-10;

or one or more polydialkoxysiloxanes having the formula:

-   -   where R is —CH₃ or —C₂H₅;

In one embodiment in the polymer above, (B) is a polydimethylsiloxanediol; and

-   -   (C) is a compound having the formula:

The ranges described in the embodiments above can have any values orsubranges therebetween. For example, wherein n is 0 to 1, referring to amixture, n can have any value therebetween, including 0, 0.01, 0.02,0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6,0.7, 0.8, 0.9, 1, any combination thereof, or any subrange therein. Thisnomenclature and equivalent versions of it are well-known in the polymerarts.

For example, wherein y is an integer of 1-1000, y may adopt any valueincluding for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50,60, 70, 80, 90, 100, 200, 250, 500, 750, 900, 1000, any combinationthereof, or any subrange therein. This nomenclature and equivalentversions of it are well-known in the polymer arts.

So long as R₁ and R₂ are not identical, each may be independently—OCH₂CF₂H, —OCH₂CF₂CF₂H, —OCH₂CF₂CF₂CF₂H, —Br, —(OC₂H₄)_(x)—O—CH₃(wherein x is 0-11, including 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11or any subrange therein), alkoxy, fluoroalkoxy, alkoxycycloalkyl, or agroup having one of the following formulas:

In the formulas described, a is 5-15 or any subrange therebetween,including 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or any subrangetherein.

In the formulas described, b is 0-5 or any subrange therebetween,including 0, 1, 2, 3, 4, 5, or any subrange therein.

In the formulas described, r is an integer of 1-10 or any subrangetherebetween, including 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or any subrangetherein.

In the formulas described, X may be any one of Cl, Br, I, OH, or NO₃ or,if more than one compound is present, each compound may have a differentX, or every compound may have the same X.

In the formulas described, A is —CO₂ or —SO₃ or, if more than onecompound is present, each compound may have a different A or everycompound may have the same A.

In the formulas described, the isocyanates and diisocyanates are notparticularly limited and, given the teachings herein combined with theknowledge of one of ordinary skill, they can be selected as appropriate.For example, methylene dicyclohexyl diisocyanate, diphenylmethanediisocyanate, hexamethylene diisocyanate, isophorone diisocyanate,toluene diisocyanate, xylylene diisocyanate, cyclohexane diisocyanate,tetramethyl xylylene diisocyanate, trimethylhexamethylene diisocyanate,norbornane diisocyanate, phenylene diisocyanate, or a combination of twoor more thereof.

Similarly, the isocyanate is not particularly limiting. Non-limitingexamples of the isocyanate include compounds having the formula:

wherein R_(D) is —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —CH₂CH₂CH₂CH₃, and p is aninteger of 1-10. The p range includes all values and subrangestherebetween, including 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11, or anysubrange therein. In one embodiment, p is 1, 2, 3, or 4.

If desired, one or more chain extenders may be used, which are notparticularly limiting. Any suitable diol or diamine chain extender maybe used. Non-limiting examples of the diol include a C₁₋₁₀ alkylenediol, C₁₋₁₀ alkenylene diol, C₁₋₂₀ aralkylene diol, 1,4-butanediol, orthe like, or combinations of two or more thereof, though others arepossible. Similarly, non-limiting examples of diamine chain extendersinclude C₁₋₁₀ alkylene diamine, C₁₋₁₀ alkenylene diamine, C₁₋₂₀aralkylene diamine, or the like or combinations of two or more thereof,though others are possible.

Similarly, in the formulas described, the diol or diamine chain extenderare not particularly limited and, given the teachings herein combinedwith the knowledge of one of ordinary skill, they can be selected asappropriate. For example, chain extending diols may include a C₁₋₁₀alkylene diol, C₁₋₁₀ alkenylene diol, C₁₋₂₀ aralkylene diol,1,4-butanediol, or the like, or combinations of two or more thereof,although others are possible. Similarly, non-limiting examples ofdiamine chain extenders include C₁₋₁₀ alkylene diamine, C₁₋₁₀ alkenylenediamine, C₁₋₂₀ aralkylene diamine, or the like, or combinations of twoor more thereof, although others are possible.

Similarly, in the formulas described, the soft block diol may besuitably chosen from known polydimethylsiloxane diols,polytetramethylene oxide diols, polypropylene oxide diols, polyethyleneoxide diols, polybutadiene diols, polyisobutylene diols, perfluorinateddiols, or a combination of two or more thereof.

HMDI/BD(30)-[(4FOx)(C12)] has the following structure:

In one embodiment, a hybrid modifier may be desirable in view ofstability. In another embodiment, the HMDI/BD(30)-[(4FOx)(C12)]polyurethane modifier exhibits a remarkable improvement over theconventional “—CF₃” copolyoxetane in view of the higher C12 (34 molepercent, p=66).

In one embodiment, the molecular weight for the P[(4FOx)(C12)] is 5.7kDa, which may suitably be determined by end group MW (¹H-NMR).

In one embodiment, the polyurethane modifier isHMDI/BD(30)-[(ME2Ox)(C12)], which may be desirable in view ofbiocompatibility and/or cytocompatibility.

In one embodiment, the polyurethane modifier isHMDI/BD(30)-[(ME2Ox)(C12)] (with 14 mol % C12).

In one embodiment, a hybrid modifier has the following formula:

In one embodiment, for above hybrid modifier, p can range from 20-80 mol% or any subrange therein. In one embodiment, p is 50 mol % but therange.

In the compounds and compositions described, usingHMDI/BD(XX)-P[(4FOx)(C12)-YY:ZZ-molecular weight] as a generic example,the “XX”, “YY”, and “ZZ” have the following meanings. XX is the weightpercent of the “hard block” component (in this example, an HMDI/BDpolyurethane, and YY is the weight percent soft block (which, in thisexample, is P(4FOx)(C12) copolyoxetane). The corresponding weightpercent of the soft block copolyoxetane is understood, wherein theweight percents of the hard block and soft block total to 100%. Theweight percents are based on those of the starting materials.

For convenience, one embodiment of a representative P[AB] diol is shownbelow:

In the soft block described above (in this example, the P(4FOx)(C12)copolyoxetane) but more generically, “P[AB], the YY:ZZ refer to the molepercents of the respective A and B components (in this example, A is4FOx oxetane co-monomer (YY), and B is the quaternised surface activeoxetane co-monomer “C12”.

The “-molecular weight” notation is that of the starting P[AB] diol.

In the polymer modifiers compounds and compositions described herein, XXmay is not particularly limited and may suitably range from 20-40, whichincludes all values and subranges therebetween, including 20, 21, 22,23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 376, 37, 38, 39, 40wt. %, or any subrange therein. From this, the corresponding weightpercent of soft block (which is not particularly limited and may rangefrom 60-80) may be easily calculated.

The YY mole percent is not particularly limited and may suitably rangefrom 20-80, which range includes all values and subranges therebetween,including 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34,35, 36, 37, 38, 39, 40, 50, 60, 70, 80 mol %, or any subrange therein.Similarly, the ZZ mole percent may range from 80-20 mol % and may beeasily calculated.

The molecular weight of the starting P[AB] diol is not particularlylimited and may suitably range from 200-10,000 Da, which range includesall values and subranges therebetween, including 200, 205, 225, 250,275, 500, 505, 510, 515, 525, 550, 575, 600, 650, 700, 750, 800, 850,900, 950, 1000, 1100, 1150, 1250, 1500, 2000, 2500, 5000, 7500, and10,000 Da, or any subrange therein.

In one embodiment, wherein P[(4FOx)(C12)] is used as the diol, YY:ZZ is66:34.

In one embodiment, wherein P[(ME2Ox)(C12)] is used as the diol, YY:ZZ is50:50.

In one embodiment, wherein P[(ME2Ox)(C12)] is used as the diol, themolecular weight may be 2500 Da.

In one embodiment, a hybrid modification may be used, in which atriethoxysilyl isocyanate is used to end-cap the diol, which is thencombined with an alkoxysilane “booster” for the siliceous domain, addedto base polyurethane solution, and drip coated or cast.

In one embodiment, amount of difunctional quaternized or zwitterionicsurface modifying agent present in the modified PDMS is not particularlylimited, and may be suitably range from 0.01 to 25 wt. %. This rangeincludes all values and subranges therebetween, including 0.01, 0.02,0.03, 0.04, 0.05, 0.06,0.07,0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.5,0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 wt. %, orany subrange therein.

In one embodiment, the amount of bis(trialkoxysilyl)alkane orpoly(dialkoxysiloxane) added to the compositions is not particularlylimited, and may suitably range from 0 to 35 wt. %. This range includesall values and subranges therebetween, including 0.01, 0.02, 0.03, 0.04,0.05, 0.06,0.07,0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.5, 0.6, 0.7, 0.8,0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35 wt. %, or anysubrange therein. One or more than one bis(trialkoxysilyl)alkane orpoly(dialkoxysiloxane) may be used. Combinations ofbis(trialkoxysilyl)alkane and poly(dialkoxysiloxane) may also be used.Typically, these can be used to “boost” the weight fraction of thesiliceous component in the surface modifier. Suchpoly(dialkoxysiloxanes) are well known and may be obtained from GelestPSI-021, Gelest PSI-023, or PSI-026. The ‘n’ subscript in thepoly(dialkoxysiloxane) can range from 1-1000, or any integertherebetween, including 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30,50, 75, 100, 200, 250, 500, 750, or any subrange therein.

The compositions may be prepared and applied to a surface or made into adevice or article to impart antimicrobial resistance. As such, oneembodiment relates to a device or an article having an antimicrobialsurface. In one embodiment, the action is of the contact kill type,wherein the antimicrobial component does not leach out of the surface,device, or article. Non-limiting examples of such articles or devicesinclude surface coating or composition suitable for painting, e.g., apaint, an adhesive, sealant, caulk, tubing, catheter, urinary catheter,intubation tube, shunt, cerebral shunt, transdermal device, surgicalimplant, artificial joint implant, medical device, bandage, dressing,fabric, clothing, utensil, food contacting surface, dental device,dental implant, breathing device, mask, tracheal implant, cannula,intravascular cannula, glove, suture material, thread, as sizing fortextile materials, and the like. The compounds and compositionsdescribed herein may be used in combination as an additive, blend,copolymer, or coating with any bulk polymer such as polyesters,polyacrylates, polyurethenes, styrene butadiene rubbers, cellulosic,cotton, and the like, or other surface such as glass.

In one embodiment, the antimicrobial resistance may be effective againstone or more of Staphylococcus aureus, Pseudomonas aeruginosa,Escherichia coli, methicillin-resistant Staphylococcus aureus,vancomycin resistant enterococci, vancomycin intermediateStaphylococcus, multiple antibiotic resistant Gram negative organisms,acinetobacter, enterobacter, mycobacterium.

One embodiment provides a method, comprising contacting (a) at least oneselected from the group consisting of polyurethane polymer, polyurethanecopolymer, or a combination thereof; and (b) a composition comprisingtetrahydrofuran and at least one alcohol selected from the groupconsisting of methanol, ethanol, propanol, isopropanol, or a combinationthereof; and thereafter separating, to produce a purified polyurethanepolymer, polyurethane copolymer, or a combination thereof.

Any of the polymers, blends, hybrid compositions, base polymers,coatings, and articles described herein can benefit from the applicationof this method.

In one embodiment, the method for purifying is carried out at atemperature of 25 to 100° C. This range includes all values andsubranges therebetween, including 25, 30, 35, 40, 45, 50, 55, 60, 65,70, 75, 80, 85, 90, 95, and 100° C.

If desired, the method for purifying additionally and optionallyincludes drying the purified polyurethane polymer, polyurethanecopolymer, or combination thereof.

The polyurethane polymer or copolymer is not particularly limited, andthe method for purifying may be suitably used on any polyurethanemoiety. For example, the polyurethane can be any of an alternatingcopolymer, periodic copolymer, statistical copolymer, random copolymer,block copolymer, diblock copolymer, triblock copolymer, branchedcopolymer, linear copolymer, star copolymer, brush copolymer, combcopolymer, crosslinked copolymer, thermoplastic elastomeric copolymer,HMDI/BD-30-(PTMO), copolymer of polyurethane and 4FOx-C12, copolymer ofpolyurethane and 3FOx, copolymer of polyurethane and 3FOx-C12, LubrizolESTANE ALR-E72A™ or a combination thereof.

The relative amounts of tetrahydrofuran and alcohol used in thepurification method are not particularly limiting. In one embodiment,the THF and alcohol may have a weight:weight ratio ranging from 90:10 to10:90. This range includes all values and subranges therebetween,including any of 90, 85, 80, 75, 70, 65, 60, 55, 50, 45, 40, 35, 30, 25,20, 15, and 10 to any of 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65,70, 75, 80, 85, and 90 (weight:weight).

The contacting time in the purification method is not particularlylimiting. In one embodiment, it may suitably range from 0.1 hr to 400hrs. This range includes all values and subranges therebetween,including 0.1, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 60,72, 96, 100, 120, 150, 180, 200, 300, and 400 hrs or any combinationthereof.

In one embodiment of the purification method, the alcohol is aqueous.

So long as it is applied to a polyurethane moiety, the purificationmethod may be used as part of a polymerization method. In oneembodiment, the polymerization method comprises purifying one or more ofa reactant oligomer, prepolymer, combination thereof, or the like asappropriate before further polymerizing. In another embodiment, thepurification method comprises purifying a resultant polymer, copolymer,combination thereof, or the like as appropriate. Combinations arepossible.

One embodiment provides a purified polyurethane polymer, copolymer, orcombination thereof produced by the purification method.

In the context of the method or products prepared thereby, for a polymerto be ‘purified’ it need not be completely or even substantiallypurified after undergoing the method. That is, it may still contain ameasurable or even substantial portion of impurities or contamination,e.g., unreacted monomers or reactants, surface active molecules, smallmolecules, water-soluble components, and the like. One way to determinewhether contaminants remain is so place the purified polymer into cleanwater for a few minutes, then interrogate that water using a dynamiccontact angle (DCA) apparatus and a clean flamed glass slide. Suchmethods are well-known in the art.

Conventional condensation cure is used to make coatings and elastomers.An additive that copolymerizes with standard polydimethylsiloxane diolsand alkoxysilane crosslinking agents concentrates at the surface of thecoating or article and generates contact antimicrobial function (norelease of biocide). The additive is selectively concentrated at thesurface of the coating or elastomeric object and is effective at a levelof 1 wt %. The additive confers highly effective contact kill ofbacteria in tests that mimic a cough, sneeze, or touch.

A recent study was done on poly(dimethylsiloxane) based coatingscontaining quaternary ammonium salt (QAS 1) moieties, exerting biocidalactivity through contact kill. A major point of concern about this studywas the use of a high weight percent (10-15%) of the trimethoxyfunctionalized alkylammonium salt (QAS 1).

The moderate biocidal activity observed for these coatings suggest thepresence of a substantial amount of the alkylammonium modifier QAS 1, inthe bulk.

We have developed a new strategy for surface modification of PDMS withcationic moieties. We have found that the presence of a dimethoxyfunctional group provides an unexpected improvement compared to QAS 1. Adifunctional alkoxy group allows incorporation of the modifier in thelinear polymer chain favoring surface concentration, and prevents itfrom getting trapped in the bulk. While not wishing to be limited bytheory, it is believed that the alkylammonium surface modifier being inthe linear chain would have greater mobility and a tendency ofconcentrating at the surface.

We have quantitatively generated a quaternary ammonium salt, which is adifunctional quaternary alkoxide (referred to herein as “SMA 1” or“QAM”), in a one-step reaction of the commercially availablechloropropyl precursor with C12 amine. Probing the efficacy of SMA 1, 1wt % was added to a 5 kDa PDMS diol followed by conventionalcondensation cure with BTSE, 8. A bacterial spray test with a 30 minexposure time gave >99% kill against Gram(−) (P. aeruginosa, E. coli)and Gram(+) (S. aureus) bacteria. Results indicate good stability in airover several months, which is surprising.

One embodiment relates to the development of new silicone antibacterialmodifiers for applications such as coatings and tubing used inbiomedical applications. One embodiment relies on surface concentrationof betaines, a specialized family of zwitterions, comprising of cationicmoiety such as quaternary ammonium species and anionic functional groupslike sulfo-, carboxy-, hydroxyl-, and phosphobetaines, and the approachis introducing a group that is “self chaperoning” or self-surfaceconcentrating into the polydimethylsiloxane (PDMS) main chain. Theresulting coating or object has a contact antibacterial surface. Themodified resin is suitable for a wide variety of applications includingtubing, implants, breathing devices, masks, tracheal implants, and thelike.

It is known that with long fluorous side chains (≥C_(f)8,C_(f)=perfluorinated carbon), replacement of terminal —CF₃ by —CF₂Hresults in decreased surface tension. For fluoromethacrylate blockcopolymers having “short” side chains (<C_(f)8) a similar reduction ofθ_(adv) and θ_(rec) is observed by substituting —CF₃ terminated sidechains with —CF₂H termination. We have found that a co-repeat unit witha —CF₂H side chain together with a co-repeat unit having a quaternaryside chain is more stable both in dry and wet conditions and is lessprone to surface phase separation.

In one embodiment, we have found that the so-called, “4FOx” (afluorinated side chain with a —CF₂H end group) instead of 3FOx, may be amore useful “chaperone” to direct the cationic antimicrobial moiety tothe surface because of its amphiphilic nature.

In one embodiment, bacteria exposed to the contact kill antimicrobialsurfaces described herein do not build up resistance to contact kill.

In one embodiment, the polydimethylsiloxane (PDMS) coatings andantimicrobial surfaces described herein result in a contact kill ofbacteria without release of biocide.

Stepwise synthesis of surface modifying additive ‘SMA 1’ and itsincorporation into PDMS elastomers.

The surface modifying additive, SMA 1 is synthesized by performing asubstitution reaction between the 3-chloropropyl dimethoxysilane 1 andN,N-dodecyldimethylamine 2, leading to replacement of the chlorine atomin 1 by the tertiary aminie. This substitution reaction incorporates aquaternary positive charge in the modifier which can then be reacted invarying weight percents with a PDMS elastomer. It is believed that thecharge bearing quaternary ammonium groups in SMA 1 may be entropicallydriven to the surface producing coatings with near surface quaternisedcationic moieties.

In one embodiment, synthesis of the quaternised PDMS compositionsinvolves a two step method. The first step involves a substitutionreaction between 3-chloropropyl dimethoxysilane 1, andN,N-dimethyldodecylamine 2. Step 2 involves a condensation reactionbetween the precursor synthesized in step 1, a crosslinking agent 3 anda low molecular weight silanol terminated PDMS.

Precursor synthesis. In one embodiment, SMA 1 may be made by reacting 5g(27.4 mmol) of the chlorosilane1 with 5.5 g (25.8 mmol) of thedodecylamine 2 in a reaction vessel at 30° C. for 48 hrs. A constantsupply of nitrogen was maintained inside the reaction flask to eliminatethe presence of any moisture since the methoxy functional groups presentin 1 are susceptible to hydrolysis. Chlorosilane 1 was taken in excesssince its high volatility enabled removal of traces of unreacted 1 undervacuum.

In one embodiment, a P-Q-C12 (a quaternised PDMS) synthesis involvesreacting various wt % of the SMA1 with a silanol terminated PDMS (4kDa), a crosslinking agent to promote the formation of a networkstructure. This reaction is allowed to take place in the presence of 0.5wt % DBTDA catalyst.

In one embodiment, minuscule amount of SMA1 in the PDMS matrix willsurface concentrate and confer antimicrobial characteristic to thepolymer.

In one embodiment, the alkyl side chain bearing a cationic charge may beentropically driven to the surface of the polymer.

Assay for antimicrobial activity. Bacterial strains of Pseudomonasaeruginosa PAO1 and Staphylococcus aureus ATCC-25904 were used forinvestigating the biocidal efficacy of PDMS doped with 0.5 wt % of SMA1.The bacterial cultures were streaked on Luria Agar plates from frozenstocks and incubated overnight at 37° C. A single colony from eachstrain was used to inoculate 6 ml of Luria Broth (LB), was grownovernight at 37° C. at 225 rpm. A starting inoculum of 10⁸-10⁹ colonyforming units per milliliter (CFU/ml) of the desired pathogen was usedfor the culture. Aliquots from the overnight culture were taken andreinoculated in a 1:100 dilution in LB.

A biocidal test was devised to simulate aerosol deposition (cough,sneeze) of pathogenic bacteria. With a sprayer designed to deliver acontrolled volume, a challenge of Pseudomonas aeruginosa (10⁷ CFU/mL)was delivered to the surface of these PDMS coatings containing 0.5 wt %of SMA1. A constant volume of 5-mg of the bacterial culture was sprayedon the coated microscope slides. The coated slides were placed in aconstant humidity (85-95%) environment. A constant humidity is importantfor testing because control experiments in ambient air showedirreproducible fractions of dead bacteria as a function of time. After30 min, the slides were placed in saline solution and vortexed for 2min. One hundred microliter aliquots and dilutions were removed andspread onto agar plates that were incubated at 37° C. for 18 h. Livebacteria (cfu's) on plates were counted to obtain the percent kill andlog reduction. A 30 minute residence time was chosen in order to achievecomplete kill. The same protocol was followed for microscope slidescoated with conventional condensation cured PDMS that served as acontrol.

Antimicrobial activity of the 0.5 wt % P-Q-C12 composition. Biocidalefficacy of the 0.5 wt % P-Q-C12 coatings have been investigated againstP. aeruginosa and S. aureus and the results have been compared with theantimicrobial activity for a conventional PDMS coated slide. One aim wasalso to investigate the biocidal efficacy of this quaternised PDMScomposition against both Gram (+ve) S. aureus and Gram (−ve) P.aeruginosa bacteria. See FIG. 2.

For S. aureus, the control slide had an average of 118 and 123 cfu,whereas the 0.5 wt % PQ-C12 slides had 30 and 46 cfu respectively.

For P. aeruginosa, the PDMS control had 331 and 305 cfu of viablebacteria, while the 0.5 wt % PQ-C12 coated slide had 66 and 87 coloniesremaining. It was observed that this surface modifier had an ˜69% killfor S. aureus and an ˜75% kill for P. aeruginosa strains.

Investigation of Varying the Weight Percent of the PQ-C12 Modifier onBiocidal Activity.

We have achieved a considerable antimicrobial activity by having 0.5 wt% of the modifier in the matrix. Varying the amounts of the cationicsurface modifier can be correlated to the biocidal efficacy of themodified PDMS.

A 1 wt % and 2 wt % of the modifier in PDMS has been used in biocidaltests to investigate their antimicrobial effectiveness. These modifiedcoatings were also tested against Escherecia coli, a Gram (−ve)bacteria, in addition to the S. aureus and P. aeruginosa.

Antimicrobial activity of the 1 wt % and the 2 wt % P-Q-C12compositions. An improvement in the antimicrobial activity of thesemodified PDMS coatings were observed on increasing the amount of surfacemodifier. A remarkable improvement in antimicrobial effectiveness hasbeen observed going from 0.5% to 1% of the PQ-C12 surface modifier. Thepercent kill for S. aureus increased from 69% to 99.3%, similarly, 99.5for P. aeruginosa. The 1% modified coatings were also very effectiveagainst E. coli, affecting a 97.8% kill in the first 30 minutes.

Results with the 2% modified PDMS coating has been achieved. It has beenobserved that the 2% modified coating affects a 98.5% kill for S.aureus, 99.6% for P. aeruginosa and 98.7% for E. coli strains.

Polyoxetanes:

Introduction. FIG. 3 depicts one embodiment of our model in surfacemodification using P[AB]-polyurethanes. It is well known thatconcentration of soft blocks occur at the air-polymer interface inpolyurethanes. FIG. 3b shows copolyoxetane soft blocks as P[AB] “bottlebrushes”. Copolyoxetane brushes have flexible main chains (T_(g)'s, −40to −60° C.) and relatively short side chain “bristles”.

Designations. Notations for base polyurethane are typified byHMDI/BD(50)-PTMO(1000) (FIG. 3c ), where HMDI is H12MDI,(4,4′-(methylene bis-(p-cyclohexyl isocyanate)), BD is 1,4-butane diol,and 50 is the wt % HMDI/BD hard block. FIG. 3a shows the 1,3-propyleneoxide main chain and side chains that comprise P[AB] copolyoxetanebottle brushes, “BB”. A and B (and sometimes C) side chain designationsare also used for soft block repeat units. By extension, bottle brushpolyurethane modifiers (BB-U) results in notations such asHMDI/BD(30)-P[(A)(B)-p:(1-p)-5.1], where P denotes ring openedstructures for repeat units A and B, p is the A mole fraction, and 5.1is the soft block M_(n) (kDa). In ring opening polymerization,simultaneous feed of A and B monomers gives random copolyoxetanes(Scheme 1). In one embodiment, the P[AB] copolyoxetanes are randomcopolymers so that the designation P[AB] is used rather than P[A-r-B].

Model polymer surface modifier, PSM. A model PSM was investigated havinga P[(3FOx)(BrOx)] copolyoxetane soft block (2 and 3, respectively). 3FOxwas essential in that study for BrOx surface concentration. For example,with 0.5 wt % P[(3FOx)(BrOx)-1:1] polyurethane modifier, Br was 2.2 atom% by XPS, but Br was at the XPS detection limit (0.1 atom %) for acontrol having a P[BrOx] polyoxetane soft block. The notion of afluorous “chaperone” for functional moiety B was thus established.

Hydantoin PSM. The conversion of hydantoin to chloramines (—N—H→—N—Cl)by bleach results in powerful oxidative antimicrobial functionality.Chloramine functionalized surfaces (e.g., fibers) are stable in air andeven to laundering. This work stimulated the preparation of acopolyoxetane with Hy4Ox 4 as a precursor to chloramine function.Surprisingly, polyurethanes with 3FOx “chaperone” A and Hy4Ox Bcopolyoxetane soft blocks had unprecedented wetting characteristics. Thedry surface was moderately hydrophilic with 70-80° advancing contactangles (θ_(adv)), while the wetted surface was hydrophobic withθ_(adv)>100°. This is opposite usual behavior by which water adsorptionor surface reconstruction results in decreased contact angles.

The original goal of introducing oxidative antimicrobial function wasattained. Less than 2 wt % of the above PSM had surface accessible N—Hconvertible to chloramine (N—Cl) with dilute bleach. The coatingseffected rapid 100% kill of sprayed on Gram+/− bacterial challenges.

P[(3FOx)(MEnOx)] copolyoxetane diols. Both random and block[(3FOx)(MEnOx)-p:(1-p)] copolyoxetane diols were prepared. Theseamphiphilic diols containing PEG-like (ME3Ox or ME7Ox, Scheme 2) and3FOx side chains were incorporated in polyurethanes (FIG. 4a ). P[A-r-B]and P[A-b-B] polyurethanes were employed as PSMs for a conventionalMDI/BD-PTMO base polyurethane (FIG. 4b ). Surface composition (XPS),morphology (AFM) and wetting behavior for the respective P[A-r-B] andP[A-b-B] polyurethane modified base polyurethane are distinctlydifferent.

Alkyl-ammonium PSMs. catheters to touch pads. Criteria were set forcontact antimicrobial elastomers and coatings: (a) no biocide leaching,(b) stability in air and water and (c) unlike —N—Cl, low or nocytotoxicity.

Coating surface modification, which uses 1 or 2% PSM with a conventional“base” polymer, has important and distinguishing features thatcontribute to intellectual merit including (a) retention of establishedbulk properties for the majority polymer (FIG. 3b ), (b) compositionaleconomy that results from using the P[AB]-soft block polyurethane as aminor constituent, and (c) potential for translation to applications.

HMDI-BD(30)-P[(3FOx)(C12)-87:13-6.5] 5, shown, was generated as a trialPSM. The matrix polyurethane HMDI/BD(50)-PTMO is shown in FIG. 3. In aspray test, 2 wt % PSM 5 provided 100% kill against a 10⁷ CFU/mL aerosolchallenge of Gram(−) (P. aeruginosa, E. coli) and Gram(+) (S. aureus)bacteria during an exposure time of 30 min (FIG. 5b ). Excellent contactantimicrobial kill was consistent with 5a surface concentration by XPSanalysis.

Stability of 2 wt % PSM 5. A series ofHMDI/BD(30)-P[(3FOx)(C12)-86:13-M_(n)] modifiers with systematic changesin M_(n) (kDa). Temporal stability of antimicrobial effectiveness waspreviously evaluated. Tests 2-3 days after drip coating reproducedprevious results (FIG. 5b ), but after two-weeks coatings gave widelyvarying results with 50% or less kill. A representative result for a 2wt % HMDI/BD(30)-P[(3FOx)(C12)-86:14] modified coating after 2 weeks isshown in FIG. 5d . Longer times gave worse results.

To begin understanding loss of antimicrobial function, surfacemorphology was investigated by TM-AFM. 3D height images (not shown) for2 wt % HMDI/BD(30)-P[(3FOx)(C12)-86:14] were observed as a function oftime. Two days after coating, the image was observed to be almostfeatureless. After 2 weeks multiple 2-3 μm features up to ˜500 nm highappear. After 8 weeks the surface is topologically complex with a highdensity of nano- and microspike features. Loss of antimicrobialeffectiveness correlates with the observed surface phase separation ofthe HMDI/BD(30)-P[(3FOx)(C12)-86:14] modifier. The phase separateddomains apparently sequester quaternary charge leading to ineffectivecontact antimicrobial kill.

Zeta potentials.

Zeta potential measurements offer a direct determination of surfacecharge. Compared to the relatively slow deactivation of quaternarycharge density in air (biotesting, AFM), streaming potentialmeasurements indicate that water accelerates loss of surface accessiblepositive charge for the series of 5-modified polyurethanes(HMDI/BD(30)-P[(3FOx)(C12)-86:14]). The unexpected temporal instabilityof quaternary charge led to a major thrust in proposed research onstabilization strategies.

New P[AB] soft block BB-polyurethane (BB-U) modifiers with improvedtemporal stability are described. In one embodiment, a facile route toquat-surface concentration for condensation cured PDMS is described.

The matrix. In one embodiment, HMDI-BD(50)-PTMO(1000) may be used as aconvenient matrix or base polyurethane. This thermoplastic polyurethaneis easily prepared (50-100 g) and unlike most tested alternatives, doesnot confuse dynamic contact angle analysis (DCA, Wilhelmy plate) bywater contamination. With a high hard block wt % HMDI-BD(50)-PTMO(1000)has a moderate strain-to-break (˜400%) and a relatively high modulus(9.7 MPa).

New bottle brushes. To help thwart phase separation, new BB-U surfacemodifiers based on two classes of P[AB] copolyoxetanes are described.Results demonstrate surface concentration without phase separation forboth, and we have found that same P[AB]

copolyoxetane diols can be used with new bottle brush-nanoglass (BB-NG)surface modifiers described herein.

i. PEG/alkylammonium copolyoxetanes, The soft block inHMDI/BD(30)-P[(ME2Ox)(C12)-0.86:0.14] is shown. This PSM was foundhighly effective in antimicrobial testing. At short times after coatingpreparation, it was nearly equivalent to the 3FOx analog 5. In thisregard, the 19 atom C12 side chain acted as a “self-chaperone”; the 13atom side chain analog “C6” was considerably less effective inbiotesting.

PEG side chain length. The initial advancing contact angle (θ_(adv),DSC) for a 2 wt % blend of HMDI/BD(30)-P[(ME2Ox)(C12)-0.86:0.14] withthe HMDI/BD(50)-PTMO-1000 base polyurethane (FIG. 2) was 94°, followedby a drop to 80° in the second cycle (total time ˜5 min).

Quat mole fraction. C12 mole fraction can increased by increasing theBBOx 6 mole fraction in the precursor P[(ME2Ox)(BBOx)-p:(1-p)] diols. Insolution, it was found that an optimum range of C12 mole fraction(0.4-0.6) was suitable for biocidal kill (lowest minimum inhibitoryconcentration, MIC).

In one embodiment, low MICs may be obtained for 40-60 mol % C12 inP[(ME2Ox)(C12)-p:(1-p)].

4FOx/alkylammonium copolyoxetanes. With long fluorous side chains(≥C_(f)8, C_(f)=perfluorinated carbon), replacement of terminal —CF₃ by—CF₂H results in decreased surface tension. For fluoromethacrylate blockcopolymers having “short” side chains (<C_(f)8) a similar reduction ofθ_(adv) and θ_(rec) is observed; low contact hysteresis was attributedto above-ambient T_(g)'s.

Compared to methacrylates, completely different wetting behavior isobserved for a polyurethane with the 4FOx polyoxetane soft block shown.A striking feature for IPDI/BD(40)-P(4FOx) is θ_(adv)˜108° (like —CF₃)but θ_(rec)˜40°, resulting in a large contact angle hysteresis(θ_(Δ)=68°). The model shown may account for the amphiphilic behavior ofthe P(4FOx) polyurethane. In air, enthalpically driven H-bonding of CF₂Hto ether moieties is believed to result in —CF₂—CF₂— groups dominatingthe surface. XPS is consistent with this view. Hydrogen bonding mayaccount for the 40° θ_(rec).

Coatings with 2 wt % HMDI/BD(30)-P[(4FOx)(C12)-p:(1-p)] were prepared,where 4FOx to C12 ratios were 86:14 and 66:34. Zeta potentials andcontact kill against PA, P. aeruginosa, by the spray test describedherein show that the zeta potential is higher for the modifier with 34mol % C12 (92.1 mV) compared to that for the one with 14 mol % C12 (68.2mV). Importantly, the zeta potential was nearly the same (±1 mV) overthe course of two runs for each of the two modified coatings (2×20min≈40 min, 10⁻³ M KBr). In keeping with the

high positive zeta potentials, high contact kill against PA was observedfor both coatings.

The “bottle brush-nanoglass” (BB-NG) surface modification includes twoprinciple components: (a) a polyoxetane BB with triethoxysilyl endgroups and (b) an alkoxysilane that together with BB chain ends compriseprecursors to a “nanoglass”, NG phase via hydrolysis and condensationreactions.

One embodiment of the BB-NG concept is illustrated in FIG. 6 with aP[AB] copolyoxetane soft block brush (see also FIG. 2). We have foundthat BB-NG surface modification is broadly applicable, as any P[AB]copolyoxetane diol or other diol can be quickly and easily converted inone step to a BB 7-analog. The BB-NG concept is related to the use ofglass and/or silicon wafers for growing functional thin films such as bycontrolled radical polymerization. For BB-NG the nanoglass domains aregenerated in situ from alkoxy end functionalized brushes and analkoxysilane nanoglass precursor.

For P[AB] copolyoxetanes, P[(ME2Ox)(C12)] and P[(4FOx)(C12)] diols areeasily converted to 7-analogs and in turn to modified basepolyurethanes.

A conversion of P[(4FOx)(C12)-64:24] diol to a 7-analog was carried out.This reaction to form the 7-analog designated 9 is shown in FIG. 6. Thiswas followed by (b) modification of base polyurethane (FIG. 2) with 1 wt% 9 and bis(triethoxysilyl)ethane (“BTSE”) (10 wt %). Biotesting withsprayed-on P. aeruginosa (1 hr residence) confirmed feasibility with100% kill. Two weeks later with tests in triplicate, 100% kill was onceagain realized indicating good temporal stability in air. This issurprising because (a) it demonstrates the general reaction of a P[AB]diol to form a 7-analog (namely 9) and (b) the surface modification of aconventional polyurethane “delivers” quaternary antimicrobial functionthat is stable with time, which is in contrast to the instability of theconventional polyurethane modifierHMDI-BD(30)-P[(3FOx)(C12)-86:13-M_(n)]. Preliminary results suggestsomewhat better stability than even the much-improved 4-FOx basedpolyurethane modifier HMDI/BD(30)-P[(4FOx)(C12)-p:(1-p)]. In thisregard, an important practical advantage is achieved byP[(4FOx)(C12)]-TES 9, which is also much simpler to prepare and has goodsolubility.

If desired, varying wt % of NG can be achieved with increasingincrements of BTSE.

In one embodiment, the BB-NG modifier may be adapted to other polymerssuch as acrylates seems likely. P[(ME2Ox)(C12)]-7 analogs will besoluble in alcohol-water mixtures while 4FOx-based precursors will besoluble in alcohols.

HO—P(3FOx)-OH+HMDI→HMDI-U-P(3FOx)-U-HMDI (I-1)   Eq 1

I-1+H₂N(CH₂)₃-PDMS-(CH₂)₃NH₂→[H₂N(CH₂)₃-PDMS—UR-HMDI]-P(3FOx)-U-HMDI_UR—PDMS—(CH₂)₃NH₂(I-2)   Eq 2

I-2+OCN—(CH₂)₃—Si(OEt)₃→I-2[UR—(CH₂)₃—Si(OEt)₃]₂ (I-3)   Eq 3

Scheme 3. “One pot” end-capping reactions with dibutyltin diacetatecatalysis giving condensation curable PDMS-3FOx-PDMS block copolymer1-3; U, urethane; UR, urea.

Surface Modification of Polydimethylsiloxane (PDMS).

Translation to applications is strongly inhibited by the presence of aC_(f)8 component that could degrade to perfluorooctanoic acid (PFOA),which is bioaccumulative. Therefore, the preparation of the hybridtriblock copolymer, PDMS-P(3FOx)-PDMS is noteworthy as a “Cf-1 modifier.In one embodiment, the introduction of P[3FOx], 2, provides a “C_(f)1”modifier that is not a PFOA precursor.

A one pot three step reaction generates the condensation curablePDMS-3FOx-PDMS triblock I-3 (Scheme 3). Dibutyltin diacetate catalyzesurethane, urea, and condensation cure. Cured I-3 coatings show no hintof fluorous (oleophobic) surface properties. XPS and contact angles areidentical to a PDMS control.

Although the condensation cured triblock I-3 has a PDMS-like surface, atlow wt % I-3 triblock might modify a PDMS elastomer creating a fluoroussurface. Previously, isopropanol was used to differentiate PDMS (0°contact angle) from fluorous C_(f)8 (30-80°) surfaces. In a pilot study,condensation cured PDMS coatings with 0.1-2 wt % 1-3 had contact anglesof ≤20° with isopropanol as a probe liquid indicating a fluorous surfacecomponent. The contact angle decreased to 5° at 10 wt % suggestingP(3FOx) phase separation/aggregation that depletes fluorous surfaceconcentration.

The fluorinated polyoxetanes P(3FOx) and P(5FOx) described herein may beobtained from OMNOVA Solutions, Akron OH.

EXAMPLES Example 1 Polyurethane Purification

In a 60 mL vial, 30 grams of methanol and 6 grams of THF were mixed.Into the vial, 3 grams of polyurethane pellets (Lubrizol EstaneALR-E72A) was added. The mixture was then heated to 60° C. PU pelletsswell to at least double their original size within one hour, whichfurther coalesced into one piece overnight.

Every 24 hours, a sample was taken and dried under vacuum to removesolvents. A few dried pellets were soaked in clean water that wasconfirmed by pre-interrogation water check with flamed glass slide anddynamic contact angle (DCA, Wilhelmy plate, degrees). After at least 5minutes of soaking the purified polyurethane pellets, the water waschecked with DCA using a flamed glass slide to determine whethercontamination is present (i.e., small molecule or surface activemolecules leaching out of the purified polyurethane). After at least 5minutes of soaking, a water check with DCA and flamed glass slide isdone to check whether contamination is detected. Samples were checked at24, 48, 72, and 96 hour. The results (not shown) indicate that for PUpellets soaked in methanol/THF mixture for 96 hours, water contaminationis negligible after 96 hours.

Example 2 Polyurethane Purification

In a 200 mL vial, 100 grams of ethanol and 20 grams of THF were mixed.Into the vial, 10 grams of polyurethane pellets (Lubrizol EstaneALR-E72A) was added. The mixture was then heated to 30° C. PU pelletsswell to at least double of its original size within 24 hours. Thepellets were soaked for 2 weeks and no significant coalescence wasobserved. Ten pellets were taken out and dried under vacuum to removesolvents. Five dried pellets were soaked in clean water that wasconfirmed by pre-interrogation water check with flamed glass slide.After at least 5 minutes of soaking, a water check with flamed glassslide showed no water contamination.

Example 3 Synthesis and Characterization of Blends of HMDI/BDP[(3FOx)(C12)

Materials

Synthesis of Monomers:

Synthesis of 4FOx:3-Methyl-3-(2,2,3,3,-tetrafluoropropoxymethyl)oxetane, 4FOx, wassynthesized by replacing Br in BrOx with fluorinated alcohols usingphase transfer catalysis (TBAB). A typical synthesis involved reacting41.25 g (250 mmol) of BrOx with 46.2 g (350 mmol) of2,2,3,3,-tetrafluoropropan-1-ol with in presence of TBAB (5 g, 0.0125mmol). The mixture was heated to 60° C. in 20 ml of water. KOH (15.78 g,87%) was dissolved in water (20 ml) and added drop wise over one-hourperiod. This solution was then heated to 75° C. and stirred for 72 hr.The resulting 4FOx is separated from the aqueous layer usingdichloromethane. The resulting dichloromethane solution was dried withmagnesium sulfate and dichloromethane evaporated using a rotovap. GC-MSshowed a small percentage of BrOx. Short path distillation gave 99%+4FOxmonomer.

Synthesis of BBOx: The precursor to BBOx (Bromobutyl oxetane) is3-(hydroxymethyl)-3-methyl oxetane (HOOx) which was prepared via thepyrolysis of diethyl carbonate and 1,1,1 tris (hydroxymethyl) ethane asdescribed in the literature. BBOx was prepared from HOOx anddibromobutane via a phase transfer catalysis reaction and is alsodescribed in the literature.

Preparation of P[AB] diol: The P[AB] diol is prepared via cationic ringopening polymerization following the process described previously. Twodifferent diols of varying 4Fox:C12 ratio were prepared to study theeffect of changing the amount of quaternary ammonium on theantimicrobial properties of the surface modifier. The two differentdiols obtained were P[(4FOx)(BBOx)-0.86:0.14] andP[(4FOx)(BBOx)-0.66:0.34]. Molecular weights of the two diols werecalculated using NMR end group analysis. These diols were thenquaternized by the substitution of C—Br with N,N dimethyl dodecyl amine(C12) in acetonitrile for 18 hours. The diols are then used as softblocks for making polyurethanes using the soft block first method, werethe ratio of the hard block to soft block was 30:70 (wt/wt).

The base polyurethane was synthesized using a two-step solutionpolymerization, using PTMO (1000) as soft block and HMDI-BD as the hardblock (50 wt %).

Preparation of Blends and Coatings:

2, 1, and 0.5 wt % blends of the surface modifier in base polyurethanewere prepared. It was observed that unlike the 3FOx based P[AB]polyurethane, the 4FOx based polyurethanes were insoluble in THF. DMAC(dimethyl acetamide) was used as an alternative solvent. Blends of thePSM in DMAC and base polyurethane in THF produced fairly transparentcoatings. However, over a period of 7 days, the surface modifier wasobserved to be phase separating out of the blends. This prompted the useof DMAC as a solvent for the entire blend. Coatings were prepared bydrip coating glass slides and glass cover slips with the blend. Due tothe low volatility of DMAC, the coatings had to be heated in an oven at120° C., overnight. Transparent coatings were obtained.

Characterization:

X-Ray Photoelectron Spectroscopy: XPS spectra were studied for both 4FOxand 8FOx Polyurethanes. The measurements were carried out on the ThermoFisher Scientific ESCALAB 250 “X-ray Photoelectron spectrometer”. Thisinstrument has monochromatized Al K α X-ray and low energy electronflood gun for charge neutralization. X-ray spot size for theseacquisitions was on the order of 500 mm. Pressure in the analyticalchamber during spectral acquisition was less than 2×10-8 Ton Pass energyfor survey spectra was 150 eV. The take-off angle was 90°. The data wereanalyzed with the Thermo Avantage software (v4.40). Samples of 2, 1 and0.5 wt % blends were cut and attached to the sample holder using carbontape.

Atomic Force Microscopy: Morphological analyses of polyurethane surfaceswere carried out using a Dimension-3100 (Digital Instruments, CA) atomicforce microscope with a NanoScope V controller. Imaging was performed intapping mode using a microfabricated silicon cantilever (40 N/m, Veeco,Santa Barbara, Calif.) in air. Images were analysed using the Nanoscopev710 software.

Zeta Potential: The electrokinetic analyzer in surface analysis orSurPASS from Anton PAAR was used to investigate the zeta potential ofthe coated surfaces based on a streaming potential and streaming currentmeasurement. The Zeta Potential is measured using theHelmholtz-Smoluchowski method.

Bactericidal Test: Bacterial spray testing has been used in otherstudies of non-leaching biocidal materials and was used herein todetermine biocidal activity of the P[(4FOx)(C12)] PSM blend.

Agar plates were streaked with the desired bacteria from a stock culturekept frozen at −70° C. and incubated at 37° C. for 18-24 hrs. From thisplate a single colony was collected and used to inoculate 10 mL of luriabroth. This culture solution was incubated for 18-24 hrs at 37° C. Afterincubation, the 1:50 dilution of the culture was prepared and incubatedat 37° C. until an optical density of 0.2-0.3 was observed for 1 mL ofculture. Once the desired optical density has been achieved, the culturesolution is used in bacteria challenges.

A biocidal test was devised to deposit the bacterial solution via anaerosol spray. Using as stock bacteria concentration of 10⁶ colonyforming units (CFU)/mL, slides coated with 2 wt % and 1 wt % PSM blendswhere spray for 1 second and weighed to determine the amount of bacteriasolution deposited. Sprayed slides were then placed in a constanthumidity (85-95%) environment. Keeping the samples at constant humidityis important because control experiments in ambient air showedirreproducible fractions of dead bacteria as a function of time which islikely to the bacteria experiencing osmotic shock. After 60 min, theslides were placed in saline solution and vortex stirred for 2 min. Onehundred microliter aliquots and (×10) dilutions were removed and spreadonto agar plates that were incubated at 37° C. for 18 h. Afterincubation, bacteria colonies were counted to obtain the percent kill.

Results and Discussion:

We have developed antimicrobial polymeric coatings without affecting thebulk properties of the polymer which retain their antimicrobialproperties over a period of time. All the samples were studied forchanges in morphology both immediately after coating and also four weeksafter coating. The results obtained would be an indicator of how thecoatings would perform in real life conditions. Quantifying surfaceaccessible charge of 3FOx based polyurethane coatings by themicrofluidic capillary method has shown that a 2 wt % coating ofHMDI/BD(30)-P[(3FOx)(C12)-86:14] had a sharp fall in the surfaceaccessible positive charge within 80 seconds. This had explained theloss in antimicrobial properties of the 3FOx based coatings when testedafter two weeks of preparing the coatings.

X-Ray Photoelectron Spectroscopy:

The coatings of the blends were studied by XPS to understand the surfacecomposition. A survey spectrum for each of the blends confirmed thepresence of carbon, oxygen, fluorine and nitrogen. Table 1 givescomparison between the calculated and observed atom percentages of thefour elements. The calculated percentage assumes 100% surface modifiersoft block on the surface.

Zeta Potential measurements: 2 wt % blends of bothHMDI/BD(30)-P[(4FOx)(C12)-66:34-5.7] andHMDI/BD(30)-P[(3FOx)(C12)-86:14-4.2] were prepared and tested for theirzeta

TABLE 1 Calculated vs observed atom percentages of 0.5, 1 and 2 wt %blends of surface modifier. Observed atom % Surface modifier No of atomsCalculated percentage in blend in soft block atom % 0.5 1 2 C 13.1 72%67% 68% 65% O 2 11% 20% 21% 19% F 2.64 15% 10%  9% 13% N 0.34  2%  3% 3%  3%potential values. The results obtained are summarized in Table 2.

We found that increasing the percentage of C12 in the polyurethaneimparted a higher

TABLE 2 Zeta potentials for 2 wt % HMDI/BD(30)- P[(4FOx)(C12)-p:(1-p)] P1-p ζ (mV) 86 14 68.2 66 34 92.1positive charge on the surface. Antimicrobial tests were also carriedout on these two coatings and the results showed that while theHMDI/BD(30)-P[(4FOx)(C12)-66:34-5.7] showed a 100% kill of bacteria,HMDI/BD(30)-P[(3FOx)(C12)-86:14-4.2] caused 90% kill. Based on thesepreliminary data, detailed Zeta Potential measurements were carried outfor 2, 1 and 0.5 wt % blends of HMDI/BD(30)-P[(4FOx)(C12)-66:34-5.7].The results obtained are summarized in FIG. 7.

The results show a very clear distinction in the surface accessiblepositive charge for the 2, 1 and 0.5 wt % of the blends. It is believedthat the fluorous side chain of the soft block acts as a chaperone forthe quaternary ammonium side chain to be on the surface, hence,increasing the amount of C12 increases the positive charge on thesurface. A surprising observation is that the 2 wt % blend givespositive zeta potential values even after 3 hours of exposure to theelectrolyte. This is a significant improvement over what had beenpreviously observed for the 2 wt % coatings ofHMDI/BD(30)-P[(3FOx)(C12)-86:14].

The coatings were again tested after 4 weeks to see if they had lost thesurface accessible positive charge. The results are summarized in FIG.8.

Atomic force microscopy—To understand the surface morphology withchanging surface modifier concentration, TM-AFM images of 0.5 wt %, 1 wt% and 2 wt % blends were obtained. The images were obtained at asetpoint ratio of 0.9 and an area of 25 μm×25 μm was investigated. Theimages (not shown) were obtained within one week of coating of thesamples. It was observed that surface roughness increases withincreasing percentage of surface modifier in the blend. In previousstudies of evolving surface morphologies ofHMDI/BD(30)-P[(3FOx)(C12)-86:14], it was shown that not only does thesurface phase separates within three to four days of preparing thecoatings, but the phase separation is extremely dynamic with micropeaklike features appearing and multiplying on the surface over a period oftime, and within 8 weeks of coating the surface is completely coveredwith these features.

To analyze the surface stability of the new coatings, the samples wereinvestigated under similar conditions and the images obtained (notshown) show no significant change in the surface morphology over time,which is surprising.

Antimicrobial tests: Antibacterial tests were performed on the threedifferent concentrations of the blend. The results are shown in FIGS. 9and 10.

Example 4 Blends of P[4FOx:C12-66:34] diol BTSE Hybrid

Polymer surfaces modified with polyurethanes containingP[(3FOx):(C12)m:n] polyoxetane soft blocks (where 3FOx is atrifluoroethoxy side chain and C12 is the quaternary ammonium containingside chain) have the ability to kill bacteria via non-leeching contactkill.

However, further research showed the dynamic nature of these surfacesand the antimicrobial property was found to be diminished over time.Streaming potential studies on these surfaces showed the rapid loweringof surface accessible positive charge from 140mv to 85 mv within aperiod of 80 seconds for a 2 wt % blend. Changing the fluorinated sidechain from a —CF₃ group to a —CF₂CF₂H group was found to be an effectivesolution for increasing the stability of the positive charge on thesurface. It was however observed that although the change in thefluorinated side chain remarkably improved the surface stability ofpositive charge, it did not completely “lock” the positive charge on thesurface. Zeta potential studies showed the diminishing positive chargeof about 10 mv over a period of 3 hours for a 2 wt % blend of polymersurface modifier with base polyurethane. The antimicrobial property,which was excellent (100% kill) for surfaces tested within 1 week ofpreparation of the blend, was found to be reduced over a period of onemonth. Hence a simple modification of the surface was tested tostabilize the charge on the surface by restricting the movement of theside chains. Guided by the fact that surface modifier polyurethanes madefrom P[(4FOx)(C12)-66:34] showed good antimicrobial properties, it wasdecided to test the concept with the same diol.

Experiment:

Materials: P[4FOx:C12-66:34] diol was prepared according to the methoddiscussed earlier. 3-isocyanatopropyltriethoxysilane (SII 6455) andbis(triethoxysilyl)ethane (SIB 1817, BTESE) were purchased from Gelest,Inc. Dibutyltin diacetate was used as a catalyst and was purchased fromAldrich. Tetrahydrofuran, 99.6%, (for analysis ACS, stabilized with BHT)was obtained from Acros.

The reaction takes place in two steps:

FIG. 11 gives a schematic of step 1 of the preparative procedure:

In step 1, the diol is end-capped with isocyanatopropyltriethoxysilane.A 1:2 molar ratio of diol and the silane is used as the reactant. Asolution of isocyanatopropyl triethoxysilane in THF was prepared in a100 ml round bottom flask in the presence of DBTDA (0.5 wt %) catalyst(Solution A). The solution of the diol in THF was added dropwise tosolution A under dry nitrogen purge. The disappearance of the isocyanatepeak was studied at intervals to ensure 100% endcapping of the diol.

Step 2 includes of preparation of three different blends of theendcapped diols with base polyurethane. In the first step, calculatedquantities of the end capped diol is added to an alkoxysilane (BTSE).The latter, together with end caps are precursors to the “nanoglass”domain via hydrolysis and condensation reaction. The solutions were thenadded to a 20 wt % solution of base polyurethane in THF.

Three different blends of base polyurethane with 0.5, 1 and 2 wt %endcapped diol were prepared. 10 wt % BTSE was added in each case.

Base polyurethane for this reaction was synthesized using a two-stepsolution polymerization, using PTMO (1000) as soft block and HMDI-BD asthe hard block (50 wt %).

Coatings with the resulting solution were prepared within 15 min of Step2. Microscope slides and glass cover slips were drip coated for zetapotential, AFM measurements and antimicrobial tests respectively. Dipcoated slides were prepared for studying wetting behavior of samples viadynamic contact angle measurements.

Cure was overnight at ambient temperature followed by 100° C. for 24 hr.

Zeta Potential measurements: The electrokinetic analyzer in surfaceanalysis or SurPASS from Anton PAAR was used to investigate the zetapotential of the coated glass slides based on a streaming potential andstreaming current measurement. The electrolyte used was 0.1 mmol NaBrsolution. The choice of electrolyte was governed by the presence of acommon anion (Br⁻) in the polyurethane so that secondary factors such asanion exchange do not interfere with the results.

Bactericidal Test: Bacterial spray testing has been used in otherstudies of non-leaching biocidal materials and was the used to determinebiocidal activity of the P[(4FOx)(C12)] PSM blend.

Agar plates were streaked with the desired bacteria from a stock culturekept frozen at −70° C. and incubated at 37° C. for 18-24 hr. From thisplate a single colony was collected and used to inoculate 10 mL of Luriabroth. This culture solution was incubated for 18-24 hr at 37° C. Afterincubation, the 1:50 dilution of the culture was prepared and incubatedat 37° C. until an optical density of 0.2-0.3 was observed for 1 mL ofculture. Once the desired optical density has been achieved, the culturesolution is used in bacteria challenges.

A biocidal test was devised to deposit the bacterial solution via anaerosol spray. Using as stock bacteria concentration of 10⁶ colonyforming units (CFU)/mL, slides coated with 2 wt %, 1 wt % and 0.5 wt %blends where sprayed for 1 sec and quickly weighed to estimate theamount of bacteria solution deposited. Sprayed slides were then placedin a constant humidity (85-95%) environment. Keeping the samples atconstant humidity is important because control experiments in ambientair showed irreproducible fractions of dead bacteria as a function oftime which is likely to the bacteria experiencing osmotic shock. After60 min, the slides were placed in saline solution and vortex stirred for2 min. One hundred microliter aliquots and (×10) dilutions were removedand spread onto agar plates that were incubated at 37° C. for 18 h.After incubation, bacteria colonies were counted to obtain the percentkill.

Results and Discussion:

Atomic Force Microscopy:

A study of the topology and morphology provides an idea of the extent ofphase separation, if any, of the blends and hence can provide importantinformation about their performance over a period of time. Images (notshown) were taken at a setpoint ratio (r_(sp)) of 0.9 with a scan sizeof 25 μm. Two sets of images were studied to observe the change in themorphology of the surfaces with time. Images of surfaces of the blendsobtained within 1 wk of coating indicated near surface phase separationfor all the three blends with the 1 wt % blend exhibiting maximumroughness. The size of phase separated features is observed to beincreasing with the increase of the percentage of surface modifier inthe blend.

X-Ray Photoelectron spectroscopy: Elemental composition of the surfacewas studied with the help of X-Ray photoelectron spectroscopy. Table 3with the calculated and observed percentages of the elements is givenbelow. The calculated percentage assumes 100% of the fluorinated diol tobe on the surface irrespective of the composition of the blend.

TABLE 3 Calculated vs observed atomic percentages of elements on thesurface of blends Observed composition Calculated composition of blends(at %) (at %) Soft Block only Hybrid 0.5 1 2 O 11.06 19.4 25.97 20.7423.29 C 72.46 58.48 56.85 63.42 59.03 F 14.6 7.32 4.64 6.97 8.55 Si 08.31 11.6 7.39 7.41 N 1.88 6.49 0.94 1.48 1.73

From the above data it is observed that the observed percentage ofnitrogen is lower than the calculated amount. It is also observed thatincreasing the percentage of the surface modifier diol increases theavailability of nitrogen on the surface.

Zeta Potential:

Measuring and relating surface accessible positive charge to theantimicrobial property of a blend is a unique and much less timeconsuming process that helps assess not only the bactericidal propertyof a blend but also the durability of the blend. The presence ofquaternary ammonium on the surface was already confirmed by XPS.Stability of the positive charge on the surface was studied by analyzingthe surface by continuous flow of electrolyte for a period of 3 hours.The results are shown in FIG. 12.

The zeta potential values show excellent stability of the blends overtime. For the 2 wt % blend the zeta potential remains almost constantfor a period of three hours within which eight individual runs of 2cycles each were carried out. Zeta potential increases about by about 7mV for 1 wt % blends while the 0.5 wt % blend proves to be only slightlybetter than a control sample of base polyurethane. This explains theabsence of measurable quaternary ammonium nitrogen for the 0.5 wt %blend as observed by XPS.

Example 5 Quaternary Ammonium Modified Silicones

Materials. Hydroxyl terminated polydimethylsiloxane (DMS-S21, 90-120cSt, 4 kDa), 3-chloropropylmethyldimethoxysilane (SIC 2355) andbis(triethoxysilyl)ethane (SIB 1817, BTESE) were purchased from GelestInc. N,N-dodecyldimethylamine (C12) and dibutyltin diacetate wereobtained from Aldrich. Tetrahydrofuran, 99.6%, (for analysis ACS,stabilized with BHT) was obtained from Acros. Modified fumed silicananoparticles (T-FSN, Cab-o-sil TS530 HMDZ treated fumed silica) havinga BET surface area of 200 m²/g was generously provided by QuantumSilicones, Midlothian, Va.

Quaternary ammonium modifier (QAM/SMA 1) Synthesis. With reference toFIG. 13, synthesizing the modifier involves a single step. Asubstitution reaction occurs between 3-chloropropylmethyldimethoxysilane1 and N,N-dodecyldimethylamine 2 to incorporate the quaternary charge.

A typical precursor synthesis involves reacting 5 g (27.4 mmol) ofreactant 1 with 5.5 g (25.8 mmol) of the tertiary amine 2 in a reactionvessel at 30° C. for 48 hrs. The reaction was carried out in thepresence of ˜25 ml of THF as a solvent. A constant purge of dry nitrogenwas maintained inside the reaction vessel to eliminate the presence ofany moisture since the methoxy functional groups present in 1 aresusceptible to hydrolysis. The reaction of 1 with 2 provided the QAM 3in quantitative yield. A complete substitution of the chlorine atom bythe C12 tertiary amine was characterized by ¹H-NMR and FT-IRspectroscopy. The modifier was stored below room temperature inside aproperly vacuum sealed container to prevent hydrolysis of the alkoxyfunctional groups.

Coating preparation. Coatings were prepared on microscope slides byadding varying weight percents of the QAM to a silanol terminated PDMSfollowing a condensation cure. PDMS coatings with 0.5%, 1% and 2% (byweight) of the modifier were prepared for further characterization. Themodified coatings have been designated as P-x, where, ‘P’ stands for the4 kDa poly(dimethylsiloxane) and ‘x’ refers to the wt % of the surfacemodifier incorporated in the coating. Preparation of a typical 0.5 wt %modified PDMS (P-0.5) coating involves adding 0.025 g of the QAM 3 to 5g of a 4 kDa silanol terminated PDMS. The resin was mixed in high shearequipment (Speed Mixer) at 2700 rpm for 4 times at 60 seconds/cycle. Atransparent, homogenous resin was obtained to which 0.25 g (5 wt %) ofthe crosslinker, BTESE along with 0.5 wt % of DBTDA catalyst was added.The resulting resin was again mixed in high shear equipment at 2700 rpmfor 3 times at 60 sec/cycle. Microscope slides were drip coated with theresin and was kept at ambient (˜25° C.) overnight to initiate theformation of cros slinks. The condensation cure process was driven tocompletion by keeping the coated microscope slides at 100° C. for 24 hr.Plaques were formed by pouring the resin into PTFE plates and followingthe same curing technique (FIG. 14).

A representative PDMS coating reinforced with 10 wt % of fumed silicananoparticles was synthesized to investigate the effect of addingfillers on surface and bulk properties. Treated fumed silicananoparticles (0.5 g, 10 wt %) was added to 5 g of the 4 kDapoly(dimethylsiloxane) and mixed in a high shear equipment at 2700 rpmfor 60 sec. The cycle was repeated for 4 more times to obtain ahomogenous resin. The remaining process is identical to that describedin the above paragraph. These samples are designated as PR-x, where ‘PR’stands for reinforced PDMS and ‘x’ denotes the wt % modifier.

Characterization.

Infrared spectroscopy. FT-IR spectra were obtained using a Nicolet 400FT-IR spectrometer. A background spectrum was taken before running eachsample and 32 scans were taken from 500 to 4000 cm-1. The spectra wereanalyzed using Omnic software.

NMR spectroscopy. ¹H-NMR (Varian Mercury 300, 283 MHz) spectra were usedto qualitatively confirm the complete substitution of the chlorine atomfrom 1, followed by quaternisation. Spectrum for QAM samples dissolvedin chloroform-d was obtained for 32 scans.

Antimicrobial assay. Bacterial strains of Pseudomonas aeruginosa (PAO1),Staphylococcus aureus (ATCC-25904) and Escherichia coli (DH5a) were usedfor investigating the biocidal activity of P-0.5, P-1 and P-2 coatings.Condensation cured PDMS elastomer (P-0) was used as a control for thisstudy. Bacterial cultures were streaked on Luria Agar plates from frozenstocks and incubated overnight at 37° C. A single colony from eachstrain was used to inoculate 6 ml of Luria Broth (LB) and grownovernight at 37° C., 225 rpm. A starting inoculum of 10⁸-10⁹ colonyforming units per milliliter (CFU/ml) of the desired pathogen was usedfor the culture. Aliquots from the overnight culture were taken andreinoculated in LB in a 1:100 dilution.

A biocidal test was devised to simulate aerosol deposition (cough,sneeze) of pathogenic bacteria. With a sprayer designed to deliver acontrolled volume (or weight), a challenge of the bacterial culture(˜10⁷ CFU/mL) was delivered to the surface of the coated samples. Aconstant weight of ˜6 mg of the bacterial culture was sprayed on thecoated microscope slides. The coated slides were placed in a humidifiedchamber (85-95%) environment, since a constant humidity is importantbecause control experiments at ambient air showed irreproduciblefractions of dead bacteria as a function of time. This step anticipatesfuture studies for estimating kill kinetics. After 30 min residencetime, the slides were placed in saline solution and vortexed for 2 min.An 100 μl aliquot and a 1:100 dilution were removed and spread onto agarplates that were incubated at 37° C. for 18 h. Live bacteria (cfu's) onplates were counted to obtain the percent kill and log reduction. Thesame protocol was followed for microscope slides coated withconventional condensation cured PDMS that served as a control for thisstudy. Kinetics of kill was determined by altering the residence time to15 and 45 min.

Mechanical test. For tensile testing, samples were stamped out of castplaques, which were measured for thickness, width and gauge prior tomounting in the RSA III tensile clamps. Data acquisition rate was 1 Hzwhile the initial sample elongation rate was 10 mm/min. The maximumelongation at break was determined for different samples.

Results and Discussion.

Quaternary ammonium modifier (QAM) synthesis. The QAM was synthesized byfollowing a substitution reaction between3-chloropropylmethyldimethoxysilane 1 and N,N-dodecyldimethylamine 2leading to quaternization of the ammonium moiety. The presence of alkoxyfunctional groups in 1 increases its susceptibility towards hydrolysis.As a preventive measure, both inner and outer walls of the reactionvessel were properly flamed to eliminate the presence of any adheredwater molecules. The reaction was carried out in a moisture controlledenvironment by having a continuous supply of dry nitrogen through thereaction vessel. Generally, a quaternisation reaction is performed athigher temperatures (˜60° C.), but this reaction was carried out at atemperature close to ambient (˜30° C.) in order to protect the methoxygroups from hydrolysis.

Formation of the quaternary ammonium modifier was monitored andconfirmed by ¹H-NMR and IR spectroscopic analysis.

Coating preparation. As shown in FIG. 14, coating preparation involvedcondensation cure reaction between: (1) PDMS and QAM, (2) PDMS and BTESE(crosslinking agent) and between BTESE moieties themselves. Low weightpercent modifier (0.5%, 1% and 2%, by weight) were used in the coatings.FIG. 14 demonstrates a condensation cure technique, where water is botha reactant and a product. The surface modifier was physically mixed withthe hydroxyl terminated PDMS, which ensured incorporation of themodifier in the linear siloxane chain due to its difunctional methoxygroups. To further facilitate formation of crosslinks, an additionalamount of BTESE (5 wt %) was added. Condensation reaction proceeds inthe presence of trace amounts of catalyst, DBTDA (0.5 wt %) to form aslightly viscous resin. Microscope slides were drip coated and kept inthe ambient overnight to initiate the formation of crosslinks. Finally,the condensation reaction was driven to completion by placing the slidesat 100° C. for 24 hour. The resultant coatings were opticallytransparent.

Antimicrobial assay. Having established the presence of positive chargesat the polymer-air interface, the antimicrobial activity of thesecoatings was investigated against both Gram positive and Gram negativestrains of bacteria. Antimicrobial activity of the modified samples wastested for a residence time of 30 min. As compared to the control (P-0)which had 118 and 331 cfu for S. aureus and P. aeruginosa respectively,P-0.5 showed biocidal activity by affecting 68% kill against S. aureusand 75% against P. aeruginosa in 30 min. Increasing the amount ofsurface modifier to 1% (for P-1) led to an enhancement in biocidalactivity to 99.5% (SA), 99.6% (PA) and 98% (EC) as seen in FIG. 15.Within experimental error, the same extent of bacterial kill wasachieved on increasing the amount of QAM to 2% (P-2). Log reductions inbacterial cfu's follow the same trend, with the P-1 having comparativelyhigher values than P-2 for all three strains (FIG. 15).

The biocidal test result complies well with the observed streamingpotential measurements, where P-2>P-1>P-0.5>P-0. It is believed thatincreasing the weight percent of the quaternary ammonium surfacemodifier leads to an increase in the fraction of cationic groups at thesurface, which would translate to an enhanced biocidal activity. In thepresent study, the biocidal activity increased from P-0.5 to P-1whereas, and increasing the concentration of the surface modifier from1% to 2% (P-2) affects the same extent of bacterial kill (FIG. 15). Theresults demonstrate that an optimum biocidal activity is achieved at amodifier concentration of 1% (P-1), after which the antimicrobialeffectiveness stabilizes even though there is an increase in the surfacecharge density.

FIG. 16 shows the remnant number of bacterial CFUs from antimicrobialassays performed on different modified coatings and the control.

Kill kinetic assay was performed in order to determine the dependence ofbiocidal activity on residence time. A representative P-1 coatingaffected >99% kill on strains of SA, PA and EC in the first 15 min (FIG.17). The P-1 coatings show remarkable biocidal activity as compared tothe quaternized silanes which reach a 99% kill for a time >45 min. Theremnant number of bacterial CFUs after the kill kinetic assay are shownin FIG. 18.

Antimicrobial tests were also performed on the filled PDMS samplemodified with 1 wt % of the QAM. Biocidal activity of the 1 wt %modified PDMS sample decreased on adding filler (10 wt % FSN, fumedsilica nanoparticles) (FIG. 16). The percent kill ranges from 78% (PA)to 81% (EC), which is ˜20% less than the unfilled sample and there was adecrease in the log reduction by a factor of 3 (FIG. 19). It is believedthat a condensation reaction occurs between the hydroxyl moieties at thesurface of silica nanoparticles and the methoxy functional groupspresent in the QAM. This leads to FSN surface modification andsubsequent internalization of the quaternary charge, rendering thesurface with a lesser concentration of cationic charge. Silicananoparticles may be treated with hexamethyldisilazane to incorporate atrimethylsilyl group at the surface, facilitating good particledispersion. Although, in the process of silylation, a certain fractionof nanoparticle surface may remain unmodified.

From the present result it is believed that for PR-1 (filled PDMS), acondensation reaction takes place at the surface of the nanoparticlebetween fractions of remnant hydroxyl groups and the methoxy groups ofthe modifier. Immobilization of the modifier at the nanoparticle surfaceleads to internalization and their concentration at the surface of thecoating would diminish.

Mechanical property. Polydimethylsiloxane elastomers are well known fortheir low glass transition temperatures (T_(g)˜−120° C.) and highthermal stability (˜250° C.). Fumed silica nanoparticles (FSN) treatedwith hexamethyldisilazane were used as filler for the present study.

Tensile tests were done on an unfilled PDMS sample with 1 wt % of theQAM was (control) and a sample filled with 10 wt % of the treated FSN.The unfilled sample had a tensile behavior similar to a PDMS elastomer,with a maximum elongation of 45% at break. The filled sample underwent250% elongation before break (FIG. 20).

Conclusion.

The present study has shown a new route for synthesizing thermosettingsiloxane-based elastomers having antimicrobial activity. Small amounts(0.5, 1 and 2 wt %) of a surface modifier has been added to a PDMSmatrix, following a condensation reaction to concentrate positivequaternary charges at the coating surface. Streaming potential (SP), aneffective engineering technique has been utilized in this study toquantify the surface accessible quaternary charge in the modifiedcoatings. Streaming potential measurements have shown a modifierconcentration dependant charge density, with the SP increasing from P-0(unmodified control) to P-2. Antimicrobial assays have demonstratedremarkable biocidal activity for the P-1 and P-2 coatings againststrains of S. aureus, P. aeruginosa and E. coli, achieving >99% kill in30 min. Kinetics of kill was investigated for the P-1 coatings, wherethey were observed to affect >99% kill in the first 15 min. Weakmechanical property of PDMS led to reinforcing a representative P-1coating with 10 wt % of treated fumed silica nanoparticles. Animprovement in tensile property was observed with an increase inelongation at break from 45% (P-1) to 250% (PR-1). Adsorption of themodifier at the nanoparticle surface led to internalization and adecrease in surface potential and biocidal activity. Biocompatibility ofPDMS combined with antimicrobial activity would offer immense potentialfor their use in biomedical applications.

Example 6 Synthesis and Characterization of DAPMDS-PDMS-PS

Materials 1,3-Propanesultone (1,3-PS) was purchase from Sigma Aldrich.Dibutyltindiacetate (DBTDA),N,N-Dimethyl-3-aminopropylmethyldimethoxysilane (DAPMDS), silanolterminated polydimethylsiloxane (HO-PDMS-OH),1,2-bis(triethoxysilyl)ethane (BTSE), tetrahydrofuran (THF)werepurchased from Gelest and used without further purification. Themicroslides (25×75 mm, 1.0 mm thickness) used in this work werepurchased from VWR.

Synthesis of DAPMDS-PDMS-PS

The synthetic route of DAPMDS-PDMS is presented in FIG. 21.N,N-Dimethyl-3-aminopropylmethyldimethoxysilane (0.01 mol) and silanolterminated PDMS (MW=500-700; viscosity=25 cSt; 0.02 mol) were added to a100 mL round bottomed flask in the presence of 0.5% catalyst, DBTDA, andstirred under nitrogen atmosphere overnight at room temperature. TheDAPMDS contains methoxide groups which easily hydrolyze to silanolgroups, thereafter condensing with the silanol groups on the PDMS (25cSt). At the end of the reaction, methanol formed during the reactionwas removed under vacuum and the intermediate compound DAPMDS-PDMS wasobtained.

The synthetic route of DAPMDS-PDMS-PS, modifier, is presented in FIG.22. 1,3-propane sultone (0.01 mol, 1,3-PS, dissolved in ˜5 mL THF) wasadded to the stirred reaction intermediate from step 1 and left toreflux at 50° C. overnight. THF was removed by rotary evaporationfollowed by thorough removal of residual solvent under vacuum.

Preparation of Coating Finished with Modifier, DAPMDS-PDMS-PS

DAPMDS-PDMS-PS (2.0 wt %) and silanol terminated PDMS (1,000 cSt) wereintroduced into a speed-mixer vial in the presence of 25 L DBTDA, andspeed-mixed for a cycle of 60 sec at 2700 rpm. At the end of the cycle,0.5 wt % BTESE, cross-linker, was added into the vial then speed-mixedunder the same mixing condition. Under cure conditions, the silanolgroups on the modifier, HO-PDMS-OH and BTESE co-condense. The surfaceconcentration of DAPMDS-PDMS-PS imparts antimicrobial activity to thecoating. Control samples were prepared following a similar procedureexcept without the addition of modifier.

Application of Coating on Glass Slides

The finished resin was swiftly applied to glass slides to preventpremature curing while ensuring an even distribution over the surface.Any air bubbles formed during the drip-coating process were eliminated.When drip-coating was over, the glass slides were transferred into theoven at 80° C. for 24-48 h. A similar procedure was followed for thecontrol samples. When the curing was done, the antimicrobial activity ofthe coating was assessed.

Results and Discussion

¹H NMR Analysis

NMR spectra was observed for the starting materials (DAPMDS and PDMS-25cSt) through the synthesis of the intermediate compound, DAPMDS-PDMS andconfirmed the reaction between the two starting materials and theformation of modifier, DAPMDS-PDMS-PS.

Antimicrobial Properties of Coating

The antimicrobial activities of coating finished with modifier wereevaluated. The coating without the modifier was employed as a control.Bacterial colonies were allowed to grow on the surface of the coating onthe glass slides. The antimicrobial activity was assessed according totheir antimicrobial rate. FIG. 23 shows the antimicrobial activity ofcoating against P. aureus in parallel with the control. The results showa marked decrease in the bacterial viable colonies after 30 min contactof a sprayed on bacterial challenge. Up to 94% kill was found for P.aureus.

The entire contents of each of U.S. Provisional Application Ser. Nos.61/457,977, filed Jul. 26, 2011; and 61/487,991, filed May 19, 2011; andInternational Application No. PCT/US12/48425, filed Jul. 26, 2012 arehereby incorporated by reference.

This application is based on and claims priority to U.S. ProvisionalApplication Ser. Nos. 61552452, filed Oct. 27, 2011, and 61552454, filedOct. 27, 2011, the entire contents of each of which are herebyincorporated by reference.

The entire contents of each of the following articles are herebyincorporated by reference:

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1. A compound having the formula:

wherein n is 0 to 1; wherein y is an integer of 1-1000; and wherein R₁and R₂ are not identical and are each independently —OCH₂CF₂H,—OCH₂CF₂CF₂H, —OCH₂CF₂CF₂CF₂H, —Br, —(OC₂H₄)_(x)—O—CH₃, wherein x is0-11, alkoxy, fluoroalkoxy, alkoxycycloalkyl, or a group having one ofthe following formulas:

wherein a is 5-15; wherein b is 0-5 wherein X is Cl, Br, I, OH, or NO₃;and wherein A is —CO₂ or —SO₃.
 2. The compound of claim 1, having one ofthe following formulas:


3. A polymer, comprising a polymerization product of: (A) the compoundof claim 1; (B) one or more of an isocyanate, diisocyanate, orcombination thereof; (C) optionally, a diol or diamine chain extender;and (D) optionally, a diol selected from the group polydimethylsiloxanediol, polytetramethylene oxide diol, polypropylene oxide diol,polyethylene oxide diol, polybutadiene diol, polyisobutylene diol,perfluorinated diol or a combination of two or more thereof.
 4. Amethod, comprising: reacting the compound of claim 1 with one or moreisocyanates having the formula:

to produce a compound having the formula: formula:

wherein n is 0 to 1; wherein y is an integer of 1-1000; and wherein R₁and R₂ are not identical and are each independently —OCH₂CF₂H,—OCH₂CF₂CF₂H, —OCH₂CF₂CF₂CF₂H, —Br, —(OC₂H₄)_(x)—O—CH₃, wherein x is0-11, alkoxy, fluoroalkoxy, alkoxycycloalkyl, or a group having one ofthe following formulas:

wherein a is 5-15; wherein b is 0-5 wherein X is Cl, Br, I, OH, or NO₃;and wherein A is —CO₂ or —SO₃. 5-31. (canceled)